Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious complications on women's reproductive health including ectopic pregnancy, pelvic inflammatory disease and infertility. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings, including populations in resource constrained countries. In a multi-center international trial, we screened a total of 18,014 participants at baseline, 15,054 at 12 months, and 14,243 at 24 months for a variety of STDs using non-invasive molecular amplified assays. The incidence of chlamydia in men was 2.0 per 100 person years and 4.6 in women across the 5 countries. A high prevalence and incidence of asymptomatic sexually transmitted infections was identified among men and women in a wide variety of settings, prompting the need for more effective programs to identify and treat chlamydia and gonorrhea infections. We have used the Internet, www.iwantthekit.org, to offer sampling in Maryland and other areas in the U.S. for chlamydia screening in 4,500 women and over 2500 men using self-obtained vaginal swabs or self-obtained penile-meatal swabs. Prevalence for chlamydia for women has been 7.5% overall for women, and 15.3% in young women age 15-19 yr. Both young age and Black race were statistically associated with chlamydia positivity. For men, the overall prevalence has been 9.1%. Over 21% were positive for at least one STD with acceptance for collecting penile swabs being very high. Trachoma due to C. trachomatis infection is the most common cause of infectious blindness in the world. The WHO has recommended that three rounds of mass drug administration (MDA) with antibiotics be offered to control the disease in districts where the prevalence of follicular trachoma (TF) is &#8805;10% in children aged 1-9 years, with treatment coverage of at least 80%. We have participated in both surgical and antibiotic treatment intervention studies in Gambia, Niger, and Tanzania in efforts to control trachoma. To evaluate a point of care molecular diagnostic for field use we determined the sensitivity, specificity, and field utility of the Cepheid GeneXpert C. trachomatis assay for ocular chlamydia infection compared to Roche Amplicor assay. In a trachoma-endemic community in Kongwa Tanzania, 144 children ages 0 to 9 were surveyed to assess clinical trachoma and had two ocular swabs taken. Of the 144 swabs taken the prevalence of follicular trachoma by clinical exam was 43.7%, and by evidence of infection according to Amplicor was 28.5%. The sensitivity of GeneXpert for C. trachomatis when compared to Amplicor was 100% and the GeneXpert test identified more positives in individuals with clinical trachoma than Amplicor. The GeneXpert test for C. trachomatis performed with high sensitivity and specificity and demonstrated excellent promise as a field test for trachoma control. To determine whether infection recurs after mass treatment, we re-examined individuals in Tanzania five years after initiation of the program. Treatment coverage was 80% for all ages in the first year. At five years, clinical trachoma rates were lower than at baseline, ranging from 45% compared to 81% at baseline. The prevalence of trachoma decreased in a linear fashion with number of years of mass treatment, and decreased prevalence of C. trachomatis infection was related to the extent of the previous years azithromycin coverage. Our model suggests that, for communities with baseline trachoma prevalence of 50% and annual treatment coverage of 75%, >7 years of annual mass treatment will be needed to reach a prevalence of trachoma of <5%. In a sub-study of the Tanzania program, all children under 9 years in 4 villages were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study. Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40-4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25-0.80). The age group 2-4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household. None of the intervention communities met criteria to stop MDA. There was no difference in infection (2.9% vs 4.7%; P = .25) between the usual care and cessation rule communities at 18 months. In this setting, communities with low (10%-20%) initial prevalence of active trachoma did not have MDA stopped before 3 annual rounds on the basis of monitoring for infection. Infection with C trachomatis in communities with average trachoma rates at 12% to 13% cannot be eliminated before 3 rounds of MDA with azithromycin. In a companion study in Gambia the baseline prevalence of TF and of Ct infection in the target communities was much lower at 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline, or at 36 months. The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0-9 in communities randomized to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three. Thus the Gambia is close to the elimination target for active trachoma, whereas Tanzania will require prolonged MDA. In districts prioritized for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programs could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold.